Behavioral phenotypic variation in autism multiplex families: evidence for a continuous severity gradient

Abstract

Recent genetic investigations of autism have studied multiplex families, typically including families with multiple siblings who meet criteria for a diagnosis of autism. However, little is known about the specific behavioral characteristics of siblings with autism in these multiplex families. We investigated the behavioral phenotypic variability and similarity of 351 siblings with autism in 171 multiplex families using cluster analysis and correlations. The results of cluster analyses showed that the individuals with autism could be characterized on a severity gradient: a continuum based on severity of symptoms and impairment as measured by Autism Diagnostic Interview-Revised (ADI-R) scores, verbal-nonverbal status, and nonverbal IQ scores. Clusters based on scores from the ADI-R for the autism diagnostic criteria of the DSM-IV and nonverbal IQ scores still represented a severity gradient when the effects of verbal-nonverbal status were removed. The severity gradient was shown to be heritable, with a sib correlation of 30% or a heritability of 60%. In summary, in a sample of 171 autism multiplex families, there was no evidence of discrete behaviorally defined subgroups of affected individuals or families characterized by distinct patterns of behavioral symptoms. Rather, the clusters could be characterized along a single, heritable, continuous severity dimension.